Treatment of irradiated mice with high-dose ascorbic acid reduced lethality.

Treatment of irradiated mice with high-dose ascorbic acid reduced lethality.
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DOI:
10.1371/journal.pone.0117020
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Mukai Y
Mukai Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sato T;Kinoshita M;Yamamoto T;Ito M;Nishida T;Takeuchi M;Saitoh D;Seki S;Mukai Y

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抗坏血酸是一种有效的抗氧化剂和自由基清除剂。因此,预期抗坏血酸应充当辐射防护剂。我们研究了放射后抗坏血酸治疗对小鼠生存的影响。小鼠接受全身照射(WBI),然后腹腔内给予抗坏血酸。暴露后立即给予3 g/kg抗坏血酸显著增加了7至8戈伊WBI后小鼠的存活率。然而,施用少于3g/kg的抗坏血酸是无效的,并且4g/kg或更多对小鼠有害。暴露后用3 g/kg抗坏血酸处理减少了辐射诱导的骨髓细胞凋亡并恢复了造血功能。在7.5戈伊WBI后24 h(1、6、12或24 h)内用抗坏血酸(3 g/kg)治疗可有效改善小鼠存活率;然而,超过36 h的治疗无效。抗坏血酸两次处理(1.5 g/kg × 2,辐射后立即和24 h,共3 g/kg)也改善了7.5戈伊全身照射后小鼠的存活率,并抑制了辐射诱导的自由基代谢产物。总之,即使在暴露后,给予高剂量抗坏血酸也可能降低小鼠的辐射致死率。
Ascorbic acid is an effective antioxidant and free radical scavenger. Therefore, it is expected that ascorbic acid should act as a radioprotectant. We investigated the effects of post-radiation treatment with ascorbic acid on mouse survival. Mice received whole body irradiation (WBI) followed by intraperitoneal administration of ascorbic acid. Administration of 3 g/kg of ascorbic acid immediately after exposure significantly increased mouse survival after WBI at 7 to 8 Gy. However, administration of less than 3 g/kg of ascorbic acid was ineffective, and 4 or more g/kg was harmful to the mice. Post-exposure treatment with 3 g/kg of ascorbic acid reduced radiation-induced apoptosis in bone marrow cells and restored hematopoietic function. Treatment with ascorbic acid (3 g/kg) up to 24 h (1, 6, 12, or 24 h) after WBI at 7.5 Gy effectively improved mouse survival; however, treatments beyond 36 h were ineffective. Two treatments with ascorbic acid (1.5 g/kg × 2, immediately and 24 h after radiation, 3 g/kg in total) also improved mouse survival after WBI at 7.5 Gy, accompanied with suppression of radiation-induced free radical metabolites. In conclusion, administration of high-dose ascorbic acid might reduce radiation lethality in mice even after exposure.
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